A myocardial infarction (MI), or heart attack, is caused by a sudden blockage in the arteries that supply the heart muscle, known as the coronary arteries. Most of these blockages occur as a result of atherosclerosis, a process by which cholesterol and white blood cells accumulate in the wall of the artery.

Seth Bilazarian, MD's insight:

Whether reducing inflammation alone will lower vascular event rates is a major public health question. The National Heart, Lung, and Blood Institute is sponsoring a 7000-patient randomized trial called the Cardiovascular Inflammation Reduction Trial (CIRT). The study is enrolling patients in the United States and Canada at >300 centers to determine whether patients without arthritis but with known coronary disease might also benefit from LDM. CIRT is designed to test whether lowering inflammation can prevent MI and other cardiovascular events, such as stroke.

The study tests the effects of treating cardiovascular inflammation by using LDM, a safe and effective anti-inflammatory medication that does not reduce cholesterol or decrease blood pressure. LDM is a generic drug that has been widely used to treat arthritis for 40 years and has been taken safely by hundreds of thousands of adults.

CIRT is currently enrolling adults who within the past 5 years have had an MI or were diagnosed with coronary artery disease in >1 coronary artery. Patients must also have either diabetes mellitus or metabolic syndrome, 2 conditions with a high inflammatory state. For more information about the study, visit the trial website at www.theCIRT.org.

Correlation has been found between periodontal disease (PD) and stroke. This study was conducted to investigate whether dental prophylaxis and periodontal treatment reduce the incidence of ischemic stroke.

Stroke rate of non-PD subjects was 0.32%/year. In the PD group, subjects who received dental prophylaxis had the lowest stroke IR (0.14%/year); subjects with intensive treatment or tooth extraction had a higher stroke IR (0.39%/year); and subjects without PD treatment had the highest stroke IR (0.48%/year; P<0.001).

Maintaining periodontal health by receiving dental prophylaxis and PD treatment can help reduce the incidence of ischemic stroke.

Seth Bilazarian, MD's insight:

The results of this study show that periodontal disease increases the incidence of ischemic stroke, especially among the younger population. Because it can be prevented and treated with improved oral hygiene, those who already have periodontal should seek treatment to alleviate tissue inflammation and thereby reduce the incidence of ischemic stroke.

Blood test for high-sensitivity C-reactive protein (hs-CRP) —a marker for inflammation—is increasingly being used as a routine screening tool for patients who wonder if they are at risk of a heart attack or stroke. Easily done at the same time as a cholesterol screening & covered by most insurance. American Heart Association and American College of Cardiology both endorsed use of hs-CRP for "intermediate risk" individuals.

"We know that those with elevated hs-CRP are at high risk even if cholesterol levels are low, and that statin therapy can reduce the risk of heart attack and stroke in this group. While the JUPITER study showed inflammation contributes as much to cardiovascular risk as does high blood pressure or high cholesterol", Dr. Paul Ridker says "the core research question now is whether or not reducing inflammation per se will reduce that risk."

Dr. Bilazarian interviews Dr. Paul Ridker on the inflammation hypothesis and 2 ongoing trials in this area: the National Heart, Lung, and Blood Institute (NHLBI)-funded Cardiovascular Inflammation Reduction Trial (CIRT),[1] which is testing whether taking low-dose methotrexate reduces myocardial infarction (MI), stroke, or death in people with type 2 diabetes or metabolic syndrome who have had a heart attack or have stable coronary artery disease; and the Novartis-sponsored Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS),[2] which is assessing whether blocking the proinflammatory cytokine interleukin (IL)-1β with canakinumab, as compared with placebo, can reduce rates of recurrent MI, stroke, and cardiovascular death in patients post-MI with elevated high-sensitivity C-reactive protein (CRP; ≥ 2 mg/L).

Seth Bilazarian, MD's insight:

Paul Ridker provides a great primer for clinicians & patients on the status of trials investigating the links between inflammation and cardiovascular disease. He reviews the background and status of the two large randomized clinical outcomes trials he leads: CANTOS & CIRT.

Two major clinical trials are testing for the first time whether treating inflammation can reduce the risk of a heart attack or stroke, potentially opening up a new line of attack in the battle against cardiovascular disease.

Research over two decades has shown that people with chronic inflammation—detectable at low levels, for instance, with a high-sensitivity test for a marker called C-reactive protein—are at significantly higher risk of heart attack and stroke compared with those with evidence of little or no such inflammation.

These are especially high-risk patients for whom current optimal treatment often fails. "We've kind of run out of our tool kit for these individuals and yet they're still having events," said Gary Gibbons, director of the NIH's National Heart, Lung and Blood Institute, which officially funded the study.

The CANTOS trial sponsored by Novartis is testing the company's anti-inflammatory antibody called canakinumab, has already enrolled 3,000 patients of a planned 17,000 patients with stable cardiovascular disease and elevated levels of inflammation. (Ilaris is marketed for inflammatory disease called Muckle-Wells Syndrome.) In proof-of-concept studies, it yielded "provocative" evidence of benefit in coronary arteries.

Builds the case for why IL-1β inhibition is an attractive target based on experimental data and models and the current understanding of IL-1 and its potential roles in atherogenesis. Also reviews the candidate therapy, Canakinumab (Ilaris, Novartis) being investigagted in the CANTOS trial.

Brief conclusion:

Is there evidence that individuals with elevated levels of inflammatory biomarkers are at high vascular risk even when other risk factors are acceptable? => YESIs there evidence that individuals identified at increased risk due to inflammation benefit from a therapy they otherwise would not have received? => YESIs there evidence that reducing inflammation will reduce vascular events? =>

WE NEED TO FIND OUT

For patients with a prior histroy of heart attack (MI) interested in learning more about the CANTOS trial being conducted at PMA, under the direction of Dr. Sunny Srivistava in Haverhill see...

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